Extensive inter- and intra-cellular amino acid recycling poses difficulties in establishing the contributions of synthesis and degradation to overall change in tissue protein content in the whole tissue or intact organism. This research is a continuation of our studies of a novel method proposed for measuring the true rate of degradation of muscle proteins, myosin and actin, in experimental animals and human subjects. The method is based on rate at which the derived amino acid 3-methylhistidine is lost from muscle protein, following injection of a suitable labeled precursor. Changes in muscle protein degradation rates in response to various physiological and pathological conditions will be examined. Studies will be extended to human subjects. The urinary excretion of 3-methylhistidine (and its metabolite) will be measured in human subjects under a variety of physiological and pathological conditions. The rate of muscle protein turnover will be compared in a series of mammals of different body size.